Our research on the pathogenesis of cystic fibrosis is based on extensive studies of exocrine gland physiology at the levels of secretory (acinar) cell, acinus, duct and whole parotid gland of man and rat both in vivo and in vitro. We are proposing to continue the studies of metabolism, ion and organic micromolecular transport across the cell membrane, synthesis and secretory routes of macromolecules, receptor physiology and pharmacology in isolated parotid acinar cells in short term experiments in vitro. We also are developing methods of long term preservation of acinar cells under conditions of cell or tissue culture. In cystic fibrosis, we are evaluating the function of parotid acinar cells obtained from patients immediately after death and we are studying the metabolism and role of the polyamines spermine, spermidine and putrescine in exocrine glands.